Research is directed at determining mechanisms of disease caused by selected human pathogens using biologic models of infection. Development of various strains of human pathogens with the aid of recombinant DNA biotechnology provide a means to compare defined pathogen interactions with host animals under controlled experimental conditions to provide clues to how people confront persistent infections. Studies have made use of laboratory rabbits as a model animal. Investigations to determine basic immune structure and responses in rabbits demonstrate good correlation with the immunogenetics of human beings. Continued definition of the immune system is ongoing to provide more complete documentation and extrapolation of comparative immunology. Recognition of immune system function in rabbits is needed to make the system useful for studies of host response and for designing means to prevent or treat diseases. Previous work by this group as well as from other laboratories illustrate the chosen system as suited for disclosing disease mechanisms induced by a range of infectious agents including HIV-1, tuberculosis, chlamydia, papilloma viruses and HTLV-I to list a few. The investigative approach is tiered so that findings revealed either in vitro or in vivo can be manipulated and refined in the alternate modality. This approach is selected to define the biology of disease. During the past year, investigators continued comparative studies on closely related human T cell leukemia viruses (HTLV-I). The rationale involves investigating biologic consequences of infections with HTLV-I having defined genome differences, as a means of evaluating how virus primary structure might influence cellular responses and systemic pathogenesis. The experimental approach takes advantage of infectious molecular HTLV-I clones, suitable for selected mutagenesis, that were developed with the aid of a well characterized in vivo biologic infection model. Ability to evaluate the consequences of viruses generated by molecular manipulation in rabbits, provides biologic relevance to the comparative studies. In addition, investigators participated in developing a coordinated intramural program in tuberculosis research. - HLA-D Antigens/immunology; Major Histocompatibility Complex; Antigens, CD4/physiology; HIV-1/physiology; Receptors